1. Tutorial Guide : Dr. P P Lanjewar Dr.Vishal H Gosavi Transocean Offshore International Drilling Inc 19th AFIH Batch 2010-11 Roll no 09 CLI, Mumbai
2. Contents :  Introduction  Definitions  Indian Scenario & Locations of Industry in India  Categories of Pharma agents  Pharmaceutical Industrial Process  Pharmaceutical manufacturing of dosage-form products  Physical Health Hazards  Specific Health Hazards related to drugs and pharmaceuticals  Studies : Mortality & Morbidity  References
3. Introduction: General overview of Industry  The Drugs and Pharmaceutical industry develops, produces, and markets drugs licensed for use as medications.  On the surface, the industry looks clean, the white lab coats worn by workers add to the illusion of health & safety, appearances are deceptive.  Arguably the Second largest profit making industry in world  A Global industry, Pharmaceutical companies can deal in generic and/or brand medications. They are subject to a variety of laws and regulations regarding the patenting, testing and marketing of drugs.
4. Introduction: General overview of Industry  The production of medicinals demands a carefully maintained and sterile working environment  Producing drugs and other medicinals may involve exposure to toxic industrial chemicals.  As per Factory Act 1948, India - Schedule I ~ [Amendment 1987] Drugs and Pharmaceutical (Narcotics) are classified as Hazardous processes industry.  Finished products may be lifesaving medications for sick people, but they can be dangerous to healthy workers who are inhaling or absorbing them during the production process.
5. Definitions Drugs are substances with active pharmacological properties in humans and animals. Biologics are bacterial and viral vaccines, antigens, antitoxins and analogous products, serums, plasmas and other blood derivatives for therapeutically protecting or treating humans and animals. Bulks are active drug substances used to manufacture dosage- form products, process medicated animal feeds or compound prescription medications. Diagnostic agents assist the diagnosis of diseases and disorders in humans and animals. Ethical pharmaceuticals are biological and chemicals agents for preventing, diagnosing or treating disease and disorders in humans or animals.
6. Definitions Excipients are inert ingredients which are combined with drug substances to create a dosage form product. Over-the-counter pharmaceuticals are drug products sold in a retail store or pharmacy which do not require a prescription or the approval of a medical, pharmacy or veterinary professional. Pharmacy is the art and science of preparing and dispensing drugs for preventing, diagnosing or treating diseases or disorders in humans and animals. Pharmacokinetics is the study of metabolic processes relating to the absorption, distribution, biotransformation, and elimination of a drug in humans or animals. Pharmacodynamics is the study of drug action relating to its chemical structure, site of action, and the biochemical and physiological consequences in humans and animals.
7. Indian Scenario
8. Indian Scenario  In India since independence and post Globalization pharma & drugs manufacturing has sprung up very fast and still continues to grow.  It has provided a major boost and played a significant role in India’s goal of growth, self reliance, revenue earnings, employment.
9. Indian Scenario : Economic Perspective The pharma industry generally grows at about 1.5-1.6 times the Gross Domestic Product growth Globally, India ranks third in terms of manufacturing pharma products by volume The Indian pharmaceutical industry is expected to grow at a rate of 9.9 % till 2010 and after that 9.5 % till 2015 In 2007-08, India exported drugs worth US$7.2 billion in to the US and Europe followed by Central and Eastern Europe, Africa and Latin America The Indian vaccine market which was worth US$665 million in 2007-08 is growing at a rate of more than 20% The retail pharmaceutical market in India is expected to cross US$ 12-13 billion by 2012 The Indian drug and pharmaceuticals segment received foreign direct investment to the tune of US$ 1.43 billion from April 2000 to December 2008
11. Solvents Processes Solvents Processes Acetone C F B  Formaldehyde C F B Acetonitrile C F B  Formamide C Ammonia (aqueous) C F B  Furfural C n-Amyl acetate C F B  n-Heptane C F B Amyl alcohol C F B  n-Hexane C F B Aniline C  Isobutyraldehyde C Benzene C 2-Butanone (MEK) C  Isopropanol C F B n-Butyl acetate C F  Isopropyl acetate C F B n-Butyl alcohol C F B  Isopropyl ether C B Chlorobenzene C  Methanol C F B Chloroform C F B  Methylamine C Chloromethene C  Methyl cellosolve C F Cyclohexane C  Methylene chloride C F B o-Dichlorobenzene (1,2- C  Methyl formate C Dichlorobenzene)  Methyl isobutyl ketone (MIBK) C F B 1,2-Dichloroethane C B  2-Methylpyridine C Diethylamine C B  Petroleum naphtha C F B Diethyl ether C B  Phenol C F B N,N-Dimethyl acetamide C  Polyethylene glycol 600 C Dimethylamine C  n-Propanol C B N,N-dimethylaniline C N,N-dimethylformamide C F B  Pyridine C B Dimethyl sulphoxide C B  Tetrahydrofuran C 1,4-Dioxane C B  Toluene C F B Ethanol C F B  Trichlorofluoromethane C Ethyl acetate C F B  Triethylamine C F Ethylene glycol C B  Xylenes C C = Chemical synthesis, F = Fermentation, B = Biological or Natural extraction. Solvents used in the pharmaceutical industry
12. Pharmaceutical Industrial Process
13. Preparation ofPharmaceutical Product
14. Pharmaceutical manufacturing of dosage-form products
15. Occupational HazardsGeneral / PHYSICAL Hazards Specific health hazards
16. Physical Health HazardsHazards Sources of exposure Occupational Health Control to hazard effects MeasuresI. Dust Gets airborne during  Allergic reactions Use efficient manufacturing respirator & ensure they fit well  Allergic dermatitisII. Formaldehyde Used to ensure  Lung cancer  Avoid frequent Sterility of products  Hodgkins disease contact  Prostate cancer  Use of PPE  Pulmonary oedema (Acute exposures)  PneumoniaIII. Ultraviolet Used to maintain  Dry, inelastic wrinkled  Use of PPE Lamps sterility in plants skin,  Skin sores and  Skin cancer
17. Physical Health HazardsHazards Sources of Occupational exposure Health effects Control Measures to hazardIV. Ergonomics  Raw materials for  Repetitive Strain  Good Industrial & Material bulk chemical Injuries to back engineering handling mobilization  Carpal tunnel  Facility Management  Material-handling syndrome practices devices  Tendinitis  Ergonomic Design of  Heavy manual tools work  Administrative Practices (e.g. rotating workers, & worker training)
18. Physical Health HazardsHazards Sources of exposure Occupational to hazard Health effects Control MeasuresV. Rotating  Unguarded moving  Crush  Interlocked guards Machines machine parts Injuries &  Control switches Hazardous  Exposed “crush  Puncture & Energy and nip points Penetrating  Emergency stop devices Sources injuries  Loose hair, long-  Appropriate PPE sleeved clothing,  Caught jewellery between  Operator training injuries  Routine inspection and  Amputations periodic maintenance  Mechanical / Electrical Isolation procedures
19. Physical Health HazardsHazards Sources of exposure Occupational to hazard Health effects Control MeasuresVI. Noise  High sound levels  Irritability  Engineering methods : Exposures (> 85 db) Identify, Modifying,  Loss of job Enclosing & Dampening Causes : concentration noise sources. E.g :- I. Compressed air  Temporary  Employee rotation II. Vacuum sources Hearing loss program III. Ventilation systems IV. Packaging machines  Permanent  Hearing-protective Hearing Loss devices ~ Noise mapping (NIHL) (Earplugs/muffs/defenders)  Enclosed design of workplace  Noise monitoring & medical surveillance (i.e., audiometry)  Train workers
20. Specific Health Hazards related to drugs & pharmaceuticalsHazards Sources of exposure Occupational Health effects(Drug Exposures) to hazardI. Hormones Chronic / Acute Exposure Male workers: during manufacturing or Packaging  Breast development (Gynaecomastia)a) Estrogens & Female workers:derivatives  Menstrual disorders  Abnormal endometrial growth  Excessive Menopausal bleeding,  Nausea,  Headaches,  Breast pain,  Leucorrhoea  Ankle oedema
21. Specific Health Hazards related to drugs & pharmaceuticalsHazards Sources of exposure Occupational Health effects(Drug Exposures) to hazardI. Hormones (cont..) Chronic / Acute exposure Male workers: during manufacturing or Packaging  Lack of sexual drive  Testicular pain.b)Progesterone/Androgens& its derivatives Female workers:  Menstrual and ovarian function disorders  Diminished fertility  Frequent spontaneous abortions  Masculine symptoms
22. Specific Health Hazards related to drugs & pharmaceuticalsHazards Occupational Health effects(Drug Exposures)II. Antibiotics 1. Allergic reactions: Anaphylactic Shock i. Asthma ii. Skin rashes iii. Itching and redness of the eyes iv. RhinitisE.g.: -Streptomycin, 2. Vitamin deficiency: e.g.: Tetracycline, StreptomycinTetracycline, Repeated occupational exposure to antibiotics destroy normal intestinalPenicillin etc ... flora thus decreasing Vitamin absorption. 3. Fungal infections: Daily exposure to antibiotic dust can lead to fungal infections of the skin & nails. E.g.: black hairy tongue and rectal itch Women workers may develop Vaginal yeast infections 4. Toxic effects: Exposure to certain antibiotics may lead to Toxicity similar to that occur when that drug is given as medicine.
23. Specific Health Hazards related to drugs & pharmaceuticalsHazards Occupational Health effects(Drug Exposures)III. Drugs for  Headaches may be accompanied by a rapid heart beatCardiac disease and a flushed face.E.g.: Nitroglycerin  Nitrates dilate the blood vessels and make blood pressure fall.  Dizziness /Fainting  Cardiac pain / Heart attacks  Sudden death following "withdrawal" from exposure.
24. Specific Health Hazards related to drugs & pharmaceuticalsHazards Occupational Health effects(Drug Exposures)IV. Tranquilizers  Habituating and Additive : In combination with alcohol they may cause a person to loose consciousness.E.g..Diazepam etc..  In high doses, can lead to coma and death  Workers may become drowsy as a result of exposure to tranquilizers and barbiturates.
25. Specific Health Hazards related to drugs & pharmaceuticalsHazards Occupational Health effects(Drug Exposures)V. Anti Depressants Mostly affects the heart leading toE.g.  Irregular heartbeat (cardiac arrhythmias) precipitatingAmitriptyline heart conditions in production workersNortriptyline,Imipramine
26. Standards for Exposure PreventionNO OSHA standards regulating exposure to pharmaceuticals.NO Threshold Limit Values (TLVs) for pharmacologically active substances(except for acetylsalicylic acid -- a value of 5 mg/m3, 1979).Now and then threshold limits are recommended for pharmaceuticals by researchworkers, mostly in the former USSR.The almost complete absence of official data shows that it is necessary to reduceexposures to the lowest possible levels (ALARP)
27. StudiesSome researchers have concluded that it is difficult to evaluate causes of morbidityin pharmaceutical workers because manufacturing processes and additives differbetween factories and exposures are to multiple chemicals.Mortality1. A 1988 study of 826 pharmaceutical workers (USA) found increased death riskfrom cancer and suicide.Men had elevated rates of CA Colon, Kidney & CNS.Women had elevated rates of CA Breast.MorbidityMany workers develop allergic reactions to medicinals that involveBronchial sensitivity, Asthma & difficulty in breathing.It is difficult to evaluate morbidity in pharmaceutical workers because of the widediversity of chemicals used in the manufacturing process.
28. Limitations of Studies :1. Workers can be exposed to more than one drug at a time and the effects ofmultiple exposures are not known.2. The effects of short exposures to a variety of drugs may be very different fromthe effects of longer exposures to only one or two drugs.3. The routes of absorption are different. The respiratory system and skin are themain routes of entry for pharmaceuticals in the workplace.4. The gastrointestinal tract and other internal routes are the normal routes of entryfor pharmaceuticals in patients. Practically no research has been conducted onthe relationship between external dose, internal dose, and effects.
29. References :  ILO Encyclopedia of Occupational Health and Safety (4th Edition) Chapter 79 – Pharmaceutical Industry  Wikipedia Web Dictionary : Occupational Health Hazards in Drugs & Pharmaceuticals Industry.